The integrin, α6β1, is necessary for the matrix-dependent activation of FAK and MAP kinase and the migration of human hepatocarcinoma cells

V. Carloni, A. Mazzocca, P. Pantaleo, C. Cordella, G. Laffi, P. Gentilini

Research output: Contribution to journalArticlepeer-review

Abstract

Expression of the integrin, α6β1, a receptor for laminins, is associated with the progression of hepatocellular carcinoma (HCC). The approach to investigating the α6β1 integrin signaling in HCC cells was to express a deletion mutant of the β4 integrin cytoplasmic domain (β4-Δcyt) in 2 HCC cell lines, HepG2 and Huh7. Expression of this mutant prevents formation of the α6β1 heterodimer. As expected, adhesion of both the HepG2/β4-Δcyt and Huh7/β4-Δcyt transfectants to laminin, but not to collagen, was reduced compared with the mock transfectants. However, migration of the β4-Δcyt transfectants toward both collagen and laminin was inhibited, suggesting a role for α6β1 in the signaling of migration. Migration of HCC cells requires mitogenactivated protein (MAP) kinase. The adhesion of the β4Δcyt transfectants to collagen resulted in a substantial reduction in MAP kinase activation in comparison with the mock transfectants, although their ability to activate MAP kinase in response to epidermal growth factor (EGF) stimulation was not impaired. In addition, matrix adhesion of the β4-Δcyt transfectants did not stimulate the tyrosine phosphorylation of focal adhesion kinase (FAK), and this defect correlated with reduced binding of adaptor protein Grb2 to FAK. These results suggest that FAK tyrosine phosphorylation is dependent on α6β1 expression, and that FAK-Grb2 association plays a central role in α6β1-mediated activation of MAP kinase. Moreover, the expression of α6β1 in HCC cells is necessary for FAK/MAP kinase-dependent migration.

Original languageEnglish
Pages (from-to)42-49
Number of pages8
JournalHepatology
Volume34
Issue number1
DOIs
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Hepatology

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